Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers
Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers
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DOI：
10.1158/1055-9965.epi-07-0040
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发表时间：
2007-06-01
影响因子：
3.8
通讯作者：
Ambrosone, Christine B.
中科院分区：
文献类型：
--
作者：
Choi, Ji-Yeob;Neuhouser, Marian L.;Ambrosone, Christine B.
与衰老和炎症相关的氧化应激可能在前列腺癌的病因学中发挥作用。我们评估了导致活性氧中和减少的基因变异之间的潜在关联（ROS; MnSOD Ala-16 Val、CAT-262 C>T和GPX 1 Pro200 Leu）与前列腺癌风险的关系，一项在有吸烟和/或石棉暴露史的男性中预防肺癌的随机试验。采用Logistic回归分析估计比值比（OR）和95%可信区间（95%CI）。巢式病例对照分析包括具有可用DNA的研究参与者（n = 533例病例和1，470例对照），其种族，年龄和随访时间长度匹配。总体而言，MnSOD、CAT和GPX 1基因型与前列腺癌风险之间没有关联，尽管在65岁之前诊断的男性中，CAT TT基因型与风险增加相关（OR，2.0; 95%CI，0.97-3.95）。进一步的分析与环境氧化应激暴露相关的因素分层没有修改协会。当计算MnSOD、CAT和GPX 1的风险等位基因数量时，假设与ROS保护能力降低相关，与风险等位基因少于5个的男性相比，前列腺癌与携带5个或更多风险等位基因之间无显著相关性（OR，2.0; 95%CI，0.90-4.42）。总之，MnSOD，CAT或GPX 1的变体似乎对吸烟或暴露于石棉的男性队列中的前列腺癌风险没有影响，尽管氧化应激保护的累积缺陷可能导致疾病风险增加。
Oxidative stress, associated with aging and inflammation, is likely to play a role in the etiology of prostate cancer. We evaluated potential associations between gene variants that result in reduced neutralization of reactive oxygen species (ROS; MnSOD Ala-16Val, CAT -262 C>T, and GPX1 Pro200Leu) and prostate cancer risk among 724 men with incident prostate cancer who participated in the Carotene and Retinol Efficacy Trial (CARET) cohort, a randomized trial for the prevention of lung cancer among men with a history of smoking and/or asbestos exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression. Nested case-control analyses included study participants with available DNA (n = 533 cases and 1,470 controls), matched for race, age, and length of follow-time. Overall, there were no associations between genotypes of MnSOD, CAT, and GPX1 and prostate cancer risk, although among men diagnosed before age 65, CAT TT genotype was associated with increased risk (OR, 2.0; 95% CI, 0.97-3.95). Further analyses stratified by factors related to environmental oxidative stress exposures did not modify associations. When calculating the number of risk alleles of MnSOD, CAT, and GPX1 hypothetically related to reduced protection against ROS, there was a nonsignificant relationship between prostate cancer and carriage of five or more risk alleles, in comparison to men with less than five risk alleles (OR, 2.0; 95% CI, 0.90-4.42). In conclusion, it does not seem that variants in MnSOD, CAT, or GPX1 have an influence on prostate cancer risk in this cohort of men who were smokers or exposed to asbestos, although it is possible that cumulative defects in protection from oxidative stress may result in increased risk of the disease.